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Feedback loops in B-cell chromatin regulation as a therapeutic target for modulating antibody production and

Kyoko Ochiai1, Kazuhiko Igarashi2

  • 1Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

Experimental Hematology
|January 5, 2026
PubMed

Antibody maturation (involving somatic hypermutation, affinity maturation, and class switch recombination of antibody genes) occurs before plasma cell differentiation and enhances host defense against infectious agents. Various gene regulatory networks regulate antibody maturation via multiple transcription factors (TFs), which, in turn, are often regulated via different intracellular signaling pathways. BTB and CNC homolog 2 (BACH2) is an essential TF for antibody maturation as it suppresses premature plasma cell differentiation. BACH2 mainly functions as a repressor by recognizing Maf recognition elements (MAREs) and recruits repressor complexes, such as heterochromatin factors and histone deacetylation complexes, to regulatory regions. Following antigen stimulation, BACH2 expression and function are sequentially switched on and off via feedback loops during antigen-specific antibody production. This study aimed to comprehensively review the BACH2 function and regulation in B cells, including heterochromatin formation, along with the role of TFs and kinases involved in BACH2 expression and protein stability. Additionally, the review discusses the recent findings on the potential mechanisms elucidating the dynamic roles of BACH2 associated with B and/or plasma cells. Lastly, the review explores the involvement of aberrant function of BACH2 as an exacerbating factor for the onset of B-cell malignancies, along with its possible oncogenic roles and its network as a therapeutic target.

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